The present studies are concerned with the role of hormones and growth factors and their interactions with phorbol ester promoters in relationship to cell growth and differentiation with respect to neoplastic transformation in vitro and in vivo. Several systems are being utilized to study the modulation of growth factor responses and receptor levels by tumor promoters in vitro in cells maintained in serum-free, hormone-supplemented media. A variety of biological endpoints are being examined including cell proliferation, chemotaxis, extracellular matrix (ECM) production, phospholipid metabolism, prostaglandin synthesis and growth factor receptor levels. In vivo tumor promoters are being administered to carcinogen-treated rats to delineate whether, as with the production of papillomas in mouse skin, these compounds can shorten the latency period or increase the incidence of mammary adenocarcinomas.